Compositions for improving lipid metabolism

ABSTRACT

This invention aims at providing compositions and foods for improving lipid metabolism which improve the metabolism of lipids and thus are expected to contribute to the prevention and amelioration of hyperlipemia, obesity, atherosclerosis and the like. The invention provides compositions for improving lipid metabolism, compositions for preventing or treating hyperlipemia, compositions for preventing or treating obesity and foods for preventing or ameliorating hyperlipemia and obesity, which contain valine as an active ingredient.

TECHNICAL FIELD

This invention relates to compositions for improving lipid metabolismwhich improve the metabolism of lipids and thus can be expected tocontribute to the prevention and amelioration of obesity, hyperlipemia,atherosclerosis and the like. It further relates to compositions forpreventing or treating hyperlipemia and foods for preventing orameliorating hyperlipemia. It still further relates to compositions forpreventing or treating obesity and foods for preventing or amelioratingobesity.

BACKGROUND ART

In recent years, lipid intake has been increasing in Japan with thetendency toward improved and Western-style eating habits, which bringsabout a problem of excessive fat intake. The excessive fat intake causesobesity and an increase in the serum lipid level and consequentlyheightens the risk of the onset of various complications thereof (forexample, circulatory diseases, in particular, coronary and cerebralvascular accidents and life-style related diseases such as certaincancers including breast cancer and colon cancer). Thus, it becomes aserious social problem from the viewpoint of maintaining and improvingnational health.

It has been pointed out that an increase in the levels of cholesterol inthe blood is one of the risk factors of the onset of circulatorydiseases. Recently, high concentrations of triacylglycerol(triglyceride) in the blood have also attracted attention as anotherrisk factor independent from those of cholesterol.

Hyperlipemia means a condition wherein the blood cholesterolconcentration and/or the blood triacylglycerol (i.e., one of neutralfats) concentration are increased. Hypercholesterolemia(hyper-β-lipoproteinemia) with an increase in the blood cholesterollevel is caused mainly by an increase in the low-density lipoprotein(LDL, β-lipoprotein) to a level which is well known as one of the riskfactors for atherosclerosis. It is also pointed out that the excessivelipid intake results in a continuous increase in the bloodtriacylglycerol concentration and, in turn, causes the onset ofhypertriacylglycerolemia which is likely to induce atheroscleroticdiseases such as hypertension and ischemic heart disease.

Moreover, an excess in stored energy due to the excessive lipid intakecauses obesity. Obesity, which is defined as a condition with anabnormal increase in adipose in the body, is associated with an increasein visceral adipose and/or panniculus adipose. Classifications ofobesity are: obesity in the upper half of the body; obesity in the lowerhalf of the body; central obesity; peripheral obesity; visceral obesity;panniculus obesity and the like depending on the part of the body withthe increased amount of adipose.

Also, obesity is regarded as one of the causative factors of life-stylerelated diseases such as diabetes, hyperlipemia, hypertension, fattyliver, atherosclerosis, gout, myocardial infarction and angina. Peoplesuffering from these diseases sometimes develop complications dependingon the areas of adipose deposition. It has been recently clarified thatvisceral adipose deposition is associated with the highest risk.

Methods of treating hyperlipemia and obesity include dietotherapy andchemotherapy which are usually combined with kinesitherapy and healthguidance. However, these existing therapies suffer from variousdrawbacks: it is highly difficult to continue these treatments over along period of time; they are less convenient; and there is a fear ofside effects.

The percentage of patients with atherosclerosis in the total populationof Japan has been increasing constantly and it is known that abnormallipid metabolism is deeply involved in the formation of atherosclerosis.

It has been known that valine, which is one of the essential aminoacids, is usable in therapeutic agents for liver regeneration(WO96/00059) and therapeutics for hepatic diseases (WO99/16433).However, it has neither been reported nor suggested so far to use valinein improving lipid metabolism or preventing, ameliorating or treatinghyperlipemia, obesity or atherosclerosis.

DISCLOSURE OF THE INVENTION

An object of the present invention is to provide compositions forimproving lipid metabolism which improve the metabolism of lipids andthus are expected to contribute to the prevention and amelioration ofhyperlipemia, obesity (particularly visceral obesity), atherosclerosisand the like, without suffering from any of the above-describedproblems.

Another object of the present invention is to provide compositions whichare usable in the prevention and treatment of hyperlipemia, obesity andatherosclerosis. Another object of the present invention is to providefoods which can be used to assist in the prevention and amelioration ofhyperlipemia and obesity.

Based on the fact that an increase in adipose can be inhibited byadministering valine together with a high-fat diet to rats, the presentinventors have found that valine has the effect of promoting β-oxidationof lipids and inhibiting increase in adipose, thereby completing thepresent invention.

Accordingly, the present invention provides a composition for improvinglipid metabolism, which contains valine as an active ingredient.

The composition according to the present invention may be a compositionsubstantially containing valine alone as an active ingredient.

The present invention further provides a composition for preventing ortreating hyperlipemia, which contains valine as an active ingredient.

The present invention further provides a composition for preventing ortreating obesity, which contains valine as an active ingredient.

The present invention still further provides a composition forpreventing or treating atherosclerosis, which contains valine as anactive ingredient.

Furthermore, the present invention provides a food for improving lipidmetabolism, which contains valine as an active ingredient.

The present invention further provides a food for preventing orameliorating hyperlipemia, which contains valine as an activeingredient.

The present invention further provides a food for preventing orameliorating obesity, which contains valine as an active ingredient.

The present invention still further provides a food for preventing orameliorating atherosclerosis, which contains valine as an activeingredient.

It is preferable that the above-described foods are functional foods.

In the compositions or foods according to the present invention, it ispreferable that the valine is L-valine.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph showing the mean of the peritesticular adipose tissueweight of the rats of each group. In FIG. 1, an open bar stands for a 3%casein+8.4% lard group (n=3), a horizontally striped bar stands for a 3%valine+8.4% lard group (n=3), and a shaded bar stands for a normal foodgroup (n=3). Each bar shows the mean±standard deviation.

FIG. 2 is a graph showing the area of the intraperitoneal adipose tissueof a rat of each 4 weeks-feeding group calculated from the CT image. InFIG. 2, an open bar stands for a 3% casein+8.4% lard group (n=1), ahorizontally striped bar stands for a 3% valine+8.4% lard group (n=1),and a shaded bar stands for a normal food group (n=1).

FIG. 3 is a graph showing the mean of the serum triacylglycerol level ofthe rats of each group. In FIG. 3, an open bar stands for a 3%casein+8.4% lard group (n=3), a horizontally striped bar stands for a 3%valine+8.4% lard group (n=3), and a shaded bar stands for a normal foodgroup (n=3). Each bar shows the mean±standard deviation.

FIG. 4 is a graph showing the mean of the serum free fatty acid level ofthe rats of each group. In FIG. 4, an open bar stands for a 3%casein+8.4% lard group (n=3), a horizontally striped bar stands for a 3%valine+8.4% lard group (n=3), and a shaded bar stands for a normal foodgroup (n=3). Each bar shows the mean±standard deviation.

FIG. 5 is a graph showing the mean of the serum lipid peroxide level ofthe rats of each group. In FIG. 5, an open bar stands for a 3%casein+8.4% lard group (n=3), a horizontally striped bar stands for a 3%valine+8.4% lard group (n=3), and a shaded bar stands for a normal foodgroup (n=3). Each bar shows the mean±standard deviation.

FIG. 6 is a graph showing the mean of the serum β-lipoprotein level ofthe rats of each group. In FIG. 6, an open bar stands for a 3%casein+8.4% lard group (n=3), a horizontally striped bar stands for a 3%valine+8.4% lard group (n=3), and a shaded bar stands for a normal foodgroup (n=3). Each bar shows the mean±standard deviation.

FIG. 7 a is a micrograph (×100) of an HE stained section of the aorta inthe chest of a control rabbit; and FIG. 7 b is a micrograph (×100) of anHE stained section of the aorta in the chest of a valine-administeredrabbit.

BEST MODE FOR CARRYING OUT THE INVENTION

As the valine to be used in the present invention, marketed products,synthetic products and the like can be arbitrarily employed withoutlimiting the production method. Although D-, L- and DL-valines are allusable, it is particularly preferable to use L-valine.

The compositions for improving lipid metabolism according to the presentinvention exhibit an effect of improving the lipid metabolism of animals(for example, humans, rabbit and mouse) and thus are expected to exerteffects of preventing, treating or ameliorating hyperlipemia (such ashypertriacylglycerolemia and hypercholesterolemia), obesity (such asvisceral obesity and panniculus obesity, particularly visceral obesity),visceral adipose tissue syndrome and the like. It is also expected thatthese compositions contribute to the prevention, amelioration and thelike of complications of the above diseases (circulatory diseases suchas atherosclerosis and hypertension, life-style related diseases such ascertain cancers including breast cancer and colon cancer).

The compositions for preventing or treating hyperlipemia and the foodsfor preventing or ameliorating hyperlipemia according to the presentinvention are expected to be effective in preventing, treating orameliorating hyperlipemia. These compositions and foods are alsoexpected to contribute to the prevention, amelioration and the like ofvarious complications accompanying the same.

The compositions for preventing or treating obesity and the foods forpreventing or ameliorating obesity according to the present inventionare expected to be effective in preventing, treating or amelioratingobesity (particularly visceral obesity), visceral adipose tissuesyndrome and the like. These compositions and foods are also expected tocontribute to the prevention, amelioration and the like of variouscomplications accompanying the same.

In the case of administering the compositions for improving lipidmetabolism, the compositions for preventing or treating hyperlipemia orthe compositions of preventing or treating obesity according to thepresent invention to a living body, the administration can be madeeither orally or parenterally (for example, rectally, subcutaneously,intraspinally, intramuscularly, intravenously, intra-arterially andtransdermally). Oral or intravenous administration is preferable.

These compositions according to the present invention may be formulatedinto preparations of appropriate dosage forms, for example, tablets,dusts, granules, fine subtilaes, pills, capsules, troches, chewabletablets, solutions, emulsions, suspensions, suppositories and syrups.These preparations may be produced by using pharmaceutically acceptablecarriers, excipients, additives and the like.

In the case of intravenous administration, it is preferable to use thecompositions according to the present invention in the form ofsolutions, emulsions or suspensions. Solutions can be prepared by usingsolvents such as purified water, physiological saline, alcohols (such asethanol, propylene glycol, glycerol and polyethylene glycol) andtriacetin. These preparations may further contain auxiliary agents suchas preservatives, moistening agents, emulsifiers, dispersants andstabilizers.

Solid preparations such as tablets, pills, dusts, granules, finesubtilaes, troches and chewable tablets can be produced in aconventional manner with the use of, for example, carriers (such assodium bicarbonate, calcium carbonate, starch, sucrose, mannitol andcarboxymethylcellulose) and additives (such as calcium stearate,magnesium stearate and glycerol). It is also possible to produce entericpreparations by spraying solutions of enteric substances (such ascellulose acetate phthalate, hydroxypropylmethylcellulose phthalate,polyvinyl alcohol phthalate, styrene-maleic anhydride copolymer andmethacrylic acid-methyl methacrylate copolymer) in organic solvents orwater to thereby form enteric coatings. The pharmaceutically acceptablecarriers include other auxiliary agents, aromatic agents, stabilizersand preservatives commonly employed in the art if needed. Furthermore,the compositions of the present invention may be used together withtransfusion preparations or added to other transfusion preparations.

In the case of being used as medicines, the compositions according tothe present invention may be administered in various doses depending onthe sex, body type, constitution, age and condition of the patient,dosage form and the like. In general, the dose may be appropriatelyselected to give from 0.1 to 50 g/day, preferably from 1 to 25 g/day, ofvaline as an active ingredient to an adult. The administration frequencyvaries depending on the condition of the patient, dosage form or thelike. It is adequate to administer from once to several times per day.

The foods for preventing or ameliorating hyperlipemia and the foods forpreventing or ameliorating obesity according to the present inventionmay be either foods substantially containing valine on its own orproducts prepared by adding valine directly to existing foods, drinks orthe like. For example, valine can be added directly to confectioneries(such as chewing gum, candy, jelly, gummy candy, cookie, biscuit andchocolate), soft drinks (such as juice), processed milk products (suchas cheese, butter and yogurt), processed agricultural products (such asice cream and ham), processed fish products (such as chikuwa andhanpen), noodles (such as soba and udon), processed wheat flour products(such as bread and cake), canned foods, seasonings (such as salt,pepper, sugar and synthetic sweetener) and the like. It is also possibleto add valine during the manufacturing process of these food products.To produce processed foods containing valine, use can be made ofconventional food processing methods. To add valine to foods, the valinemay be used in the form of either a solid (such as powder, granules andfine subtilaes) or a liquid. The foods for preventing or amelioratinghyperlipemia and the foods for preventing or ameliorating obesityaccording to the present invention are applicable as specified healthfoods, functional foods or health foods for preventing or amelioratinghyperlipemia or obesity. The term “functional foods” means foodscontaining components having biological regulatory functions. Thefunctions of individual food products can be indicated under theapproval by the Ministry of Health, Labour and Welfare.

It is generally preferable that the foods according to the presentinvention contain from about 0.1 to 50 g of valine per 100 g. In thecase of human adults, it is generally favorable to administer such afood so as to provide a daily valine intake of 1 to 25 g, though therecommended intake level varies depending on the sex, body type,constitution and age of the subject, other foods consumed and the like.It is adequate to administer from once to several times per day.

The compositions for improving lipid metabolism according to the presentinvention are efficacious on animals other than humans. Thus, thesecompositions can be used in order to prevent excessive body fataccumulation and improve meat qualities of, for examples, domesticanimals such as cattle and pig and cultivated fishes such as yellow tailand sea bream. Moreover, these compositions are usable in the preventionor amelioration of hyperlipemia or obesity in dogs and cats; it can alsobe used for controlling the health of these pets.

The compositions for improving lipid metabolism according to the presentinvention may be given to animals by, for example, adding it to animalfeeds, fish feeds or pet foods. The form and production method of thesefeeds or pet foods can be arbitrarily selected by those skilled in theart without restriction. In general, the desired feeds or pet foods canbe easily produced by preliminarily adding valine to fats or oilsemployed as raw materials or adding valine in an appropriate manner inthe course of production. In the case of the feeds and pet foods, it isgenerally favorable to add from about 0.1 to 50 g of valine per 100 g,though the addition level varies from animal to animal.

EXAMPLE

Hereinbelow, the present invention will be illustrated in greater detailwith reference to the following Examples, which should not be construedas limiting the scope of the present invention.

Example 1

To evaluate the effects of valine on lipid metabolism, the effects ofthe administration of L-valine containing feeds were examined on maturedrat models fed with high-fat diets.

I. Experimental Method

18 Crj:CD(SD) IGS male rats aged 12 weeks (body weight: 420 to 464 g,443 g on average) were pre-fed for 5 days (not more than 4 animals/cage,temperature: 20 to 26° C., humidity: 30 to 70%, illumination: 8:00 to20:00). During the pre-feeding period, the animals were maintained on afeed (constant feeding) and water (using a water supplier) as desired.

After the completion of the pre-feeding, the animals were divided into 6groups depending on feed and administration period. Rats of valine+lardgroups were fed with a solid feed prepared by adding 8.4% lard (CAMERIA:manufactured by Romi Smilfood B. V.) and 3.0% L-valine (JP, manufacturedby Ajinomoto Co., Inc.) to a conventional feed (CMF: manufactured byOriental Yeast Co., Ltd.) for 2 or 4 weeks. Animals of casein+lardgroups (i.e., control groups) were fed with a solid feed prepared byadding 8.4% lard and 3.0% milk-origin casein (manufactured by Wako PureChemical Industries, Ltd.) to the conventional feed (CMF: manufacturedby Oriental Yeast Co., Ltd.) for 2 or 4 weeks. Animals of normal foodgroups were fed with a solid feed which was the conventional feed (CMF:manufactured by Oriental Yeast Co., Ltd.) for 2 or 4 weeks. During theexperimental period, the rats of each group were maintained on the feed(constant feeding) and water (using a water supplier) as desired. Eachgroup had 3 rats which were fed in a single cage (temperature: 20 to 26°C., humidity: 30 to 70%, illumination: 8:00 to 20:00) throughout theexperimental period.

After 2 or 4 weeks, the blood samples of the animals of each group werecollected from the abdominal aorta and then the animals were sacrificedby bleeding under etherization followed by autopsy. As intraperitonealadipose tissue, the adipose tissue around the left testis and epididymiswas weighed. The collected blood samples were subjected to aserobiochemical examination and the like.

22 days after the initiation of the experiment, one rat of each of the 4weeks-feeding groups was subjected to the abdominal CT scanning (slicewidth: 5 mm) under anesthesia with Nembutal. From the CT image thusobtained, the intraperitoneal adipose tissue area was determined as themean of the intraperitoneal adipose-containing areas in posterior 4slices from the sites where no kidney was observed.

II. Results

(1) Adipose Tissue Weight

FIG. 1 shows the mean of the peritesticular adipose tissue weight(around the left testis and epididymis) of the rats of each group. Inthe 2 weeks-feeding groups, the peritesticular adipose tissue weight (g)of the casein+lard group was 3.66±0.60 (mean±standard deviation, thesame will apply hereinafter), while those of the valine+lard group andthe normal food group were respectively 2.55±0.38 and 2.78±0.54. Acomparison of the data of these groups indicates that the mean adiposetissue weight of the valine+lard group was about 0.70 times as much asthat of the casein+lard group. Namely, the adipose tissue weight of thevaline+lard group was less by 30% than that of the casein+lard group.Also, the adipose tissue weight of the valine+lard group was smallerthan that of the normal food group.

In the 4 weeks-feeding groups, the adipose tissue weight (g) of thecasein+lard group was 3.97±0.78, while those of the valine+lard groupand the normal food group were respectively 2.92±0.40 and 3.03±0.70. Acomparison of the data of these groups indicates that the mean adiposetissue weight of the valine+lard group was about 0.74 times as much asthat of the casein+lard group. Namely, the adipose tissue weight of thevaline+lard group was less by 26% than that of the casein+lard group.Also, the adipose tissue weight of the valine+lard group was smallerthan that of the normal food group.

In the 2 weeks-feeding groups, the average daily feed intakes (g) peranimal of the casein+lard group, the valine+lard group and the normalfood group were: respectively 15.7, 18.0 and 16.3 on day 1; 28.7, 24.3and 26.3 on day 7; and 25.0, 24.7 and 23.3 on day 14 (the day ofautopsy). Namely, similar data were observed among these 3 groups of 2weeks-feeding. In the 4 weeks-feeding groups, the average daily feedintakes (g) per animal of the casein+lard group, the valine+lard groupand the normal food group were: respectively 13.0, 18.7 and 16.7 on day1; 26.3, 25.3 and 27.7 on day 7; 25.3, 25.0 and 26.7 on day 14; 25.7,24.3 and 25.3 on day 21; and 24.0, 23.7 and 27.0 on day 28 (the day ofautopsy). Namely, similar data were observed among these 3 groups of 4weeks-feeding.

As discussed above, the increase in the adipose tissue weight wasinhibited in the rats fed with the feed containing valine, both in the2-weeks feeding group and the 4 weeks-feeding group, though the feedintake data of the groups were almost the same.

(2) Intraperitoneal Adipose Tissue Area

FIG. 2 shows the area of the intraperitoneal adipose tissue of a rat ofeach 4 weeks-feeding group calculated from the CT images of theabdominal part of the rat. The intraperitoneal adipose tissue areas(cm²) of the rats of the casein+lard group, the valine+lard group andthe normal food group were respectively 4.9, 3.2 and 1.9. Theintraperitoneal adipose tissue of the valine+lard group was about 0.65times as much as that of the casein+lard group. As discussed above, thefeed intake data of the groups were almost the same. However, theincrease in the intraperitoneal adipose tissue area was more inhibitedin the rats fed with the feed containing valine than in the casein+lardgroup.

(3) Serobiochemical Examination

(i) Triacylglycerol

FIG. 3 shows the mean serum triacylglycerol level of the rats of eachgroup. In the 2 weeks-feeding groups, the mean triacylglycerol levels(mg/dL) of the casein+lard group, the valine+lard group and the normalfood group were respectively 95.7±36.7, 52.0±21.9 and 48.3±14.7. Namely,the mean triacylglycerol level (mg/dL) of the valine+lard group wasabout 0.54 times as much as that of the casein+lard group.

In the 4 weeks-feeding groups, the mean triacylglycerol levels of thecasein+lard group, the valine+lard group and the normal food group wererespectively 113.7±13.2, 67.7±33.5 and 94.0±73.3. Namely, the meantriacylglycerol level of the valine+lard group was about 0.60 times asmuch as that of the casein+lard group.

(ii) Free Fatty Acid

FIG. 4 shows the mean serum free fatty acid level of the rats of eachgroup. In the 2 weeks-feeding groups, the mean free fatty acid levels(mEq/L) of the casein+lard group, the valine+lard group and the normalfood group were respectively 0.48±0.01, 0.35±0.06 and 0.31±0.01. Namely,the mean free fatty acid level of the valine+lard group was about 0.73times as much as that of the casein+lard group.

In the 4 weeks-feeding groups, the mean free fatty acid levels of thecasein+lard group, the valine+lard group and the normal food group wererespectively 0.44±0.14, 0.36±0.11 and 0.32±0.04. Namely, the mean freefatty acid level of the valine+lard group was about 0.82 times as muchas that of the casein+lard group.

(iii) Lipid Peroxide

FIG. 5 shows the mean serum lipid peroxide level of the rats of eachgroup. In the 2 weeks-feeding groups, the mean lipid peroxide levels(nmol/dL) of the casein+lard group, the valine+lard group and the normalfood group were respectively 2.6±1.5, 1.1±0.7 and 0.5±0.1. Namely, themean lipid peroxide level of the valine+lard group was about 0.42 timesas much as that of the casein+lard group.

(iv) β-Lipoprotein

FIG. 6 shows the mean serum β-lipoprotein level of the rats of eachgroup. In the 2 weeks-feeding groups, the mean β-lipoprotein levels(mg/dL) of the casein+lard group, the valine+lard group and the normalfood group were respectively 63.0±27.8, 33.3±14.5 and 25.0±6.0. Namely,the mean β-lipoprotein level of the valine+lard group was about 0.53times as much as that of the casein+lard group.

In the 4 weeks-feeding groups, the mean β-lipoprotein levels of thecasein+lard group, the valine+lard group and the normal food group wererespectively 66.0±7.8, 41.0±10.8 and 36.3±23.1. Namely, the meanβ-lipoprotein level (mg/dL) of the valine+lard group was about 0.62times as much as that of the casein+lard group.

As described above, the valine+lard groups showed decreases in the lipiditems (such as triacylglycerol, β-lipoprotein and free fatty acid) inthe serobiochemical examination. Also, the valine+lard group showed adecrease in lipid peroxides which are considered one of the causativefactors of various vascular lesions and have been clarified as beingcarcinogenic.

Example 2

In order to evaluate the efficacy of valine on atherosclerosis and fattyliver, an L-valine containing feed was administered to a rabbitatherosclerotic model and its effect was investigated.

I. Experimental Method

Nine New Zealand White male rabbits aged 8 weeks (average body weight,2.06 kg) were divided into three groups (n=3) by feed and fed for 13weeks (temperature, 20 to 26° C.; humidity, 30 to 70%; illumination,8:00 to 20:00). The untreated group was given an ordinary feed (NOSANfeed for laboratory animals, LABOR STOCK, manufactured by Nihon NosanKogyo, K.K.). As for the atherosclerotic model, the control group wasgiven the ordinary feed plus 0.2% cholesterol (manufactured by Wako PureChemical Industries, Ltd.), and the valine group was given the ordinaryfeed plus 0.2% cholesterol plus 3.0% L-valine (JP, manufactured byAjinomoto Co., Inc.). Throughout the experiment, the rabbits of eachgroup were maintained on the feed (constant feeding) and water (using awater supplier) as desired.

After 13 weeks, blood samples were collected from the abdominal aorta ofthe animals of each group under etherization and the animals were thensacrificed by bleeding. By subsequent autopsy, the degree ofatherosclerotic lesion (plaque formation) in thoracic aorta and thedegree of fatty liver were compared. Sections of the thoracic aorta andthe liver were also prepared and examined histopathologically forintimal thickening and the formation of fat droplets.

II. Results

(1) Plaque Formation

Table 1 shows the result of evaluation of plaque formation in specimensof the aortic arch; in Table 1, “+” denotes visible slight plaqueformation, “++” denotes visible moderate plaque formation, and “−”denotes no visible plaque formation. In the three cases of the controlgroup, moderate plaque formation was observed in the branch and nearbyareas. In the valine group, no plaque formation was visible, or plaqueformation was visible but to a lesser extent than in the control group.

TABLE 1 Result of Evaluation of Plaque Formation in Specimens of AorticArch 1 2 3 Control group ++ ++ ++ Valine group − − +(2) Intimal Thickening

Sections of the thoracic aorta were HE stained (hematoxylin-eosinstained). The control group had visible intimal thickening (FIG. 7 a)but in the valine group, intimal thickening was hardly visible (FIG. 7b).

(3) Fatty Liver

Observation of the liver with the naked eye showed that visibleyellowing of the liver (fatty liver) occurred in the control group inproportion to the level in the serum lipid test. In the valine group, noyellowing of the liver was observed, or yellowing of the liver wasvisible but to a lesser extent than in the control group.

When liver sections were HE stained, hepatocytes of the control groupwere filled with fat droplets to become swollen but in the valine group,hepatocytes contained such a small number of fat droplets that theyexperienced no visible swelling.

Thus, it was demonstrated that the degrees of plaque formation, intimalthickening and fatty liver were smaller in the valine group than in thecontrol group (atherosclerotic model). Valine is therefore anticipatedto be useful in the prevention or treatment of atherosclerosis and inthe prevention or treatment of fatty liver.

INDUSTRIAL APPLICABILITY

As discussed above, the administration of a valine-containing feed torats fed with the high-fat diet resulted in decreases in lipid items inthe serobiochemical examination. Moreover, inhibition of an increase inthe intraperitoneal adipose tissue area was observed in the CT scanningphotographic images. In addition, inhibition of the increase inperitesticular adipose tissue weight (i.e., visceral adipose) wasobserved.

Therefore, it is suggested that the compositions or foods according tothe present invention have an effect of improving the lipid metabolismand, therefore, are expected to be highly useful in clinical medicine.Compared with the conventional ones, furthermore, the compositions orfoods of the present invention are regarded as useful products forpreventing or ameliorating hyperlipemia, obesity (particularly visceralobesity), atherosclerosis or the like, seemingly carry less risk of sideeffects and can easily be taken over a long period of time.

1. A method for improving lipid metabolism in a patient in need thereof,including at least one of reducing atherosclerosis, inhibiting anincrease in intraperitoneal adipose tissue and inhibiting visceralobesity, inhibiting visceral adipose tissue syndrome, and inhibitingfatty liver, comprising administering valine to said patient in need ofsaid improving, in an amount sufficient therefor, wherein said valine issubstantially entirely L-valine and substantially entirely free of otheramino acids.
 2. The method of claim 1 wherein said patient is a patientdiagnosed as suffering from atherosclerosis.
 3. The method of claim 1,wherein said valine is administered together with a pharmaceuticalcarrier.
 4. The method of claim 1, wherein said valine is administeredat a dosage rate of 0.1 to 50 g/day.
 5. The method of claim 1, whereinsaid valine is administered at a dosage rate of 1 to 25 g/day.